Lactobacilli function as microbicides in the human vagina through production of H2O2, acids and other products which inhibit the survival and/or growth of genital pathogens. The goal of the proposed project is to evaluate the efficacy of Lactobacillus capsule in colonizing the vagina and decreasing acquisition of bacterial vaginosis. Longitudinal cohort data supports the association between lack of vaginal lactobacilli and acquisition of bacterial vaginosis. A vaginal capsule containing Lactobacillus crispatus has been developed and shown to colonize women during a phase II study. The proposed study is a double-blind placebo-controlled trial of a Lactobacillus crispatus capsule in women attending an Adolescent Medicine Clinic (n=200), the Allegheny County Health Department (n=250). Women will be followed at 3 month intervals for 1 year. The presence of genital tract infection and vaginal lactobacilli will be determined at baseline and each follow-up visit. The hypothesis is that monthly use of exogenous lactobacilli intravaginally will decrease acquisition of bacterial vaginosis. The specific aims are 1) to assess the relationship between genital infection and lack of lactobacilli in a population of women of reproductive age; 2) to assess the effect of the Lactobacillus capsule on the vaginal ecosystem (vaginal pH, lactobacilli, other microorganisms); 3) to determine whether women randomized to receive the Lactobacillus capsule have decreased acquisition of bacterial vaginosis compared to placebo-treated women after accounting for potentially confounding behaviors; 4) to evaluate the effect of the Lactobacillus capsule on acquisition of other infections including chlamydia, trichomoniasis, vulvovaginal candiddiasis, urinary tract infections and pelvic inflammatory disease; 5) assess the immunologic response to Lactobacillus crispatus among women assigned to the L. crispatus capsule versus placebo; and 6) to assess demographic, behavioral and microbiologic factors associated with loss or acquisition of H2O2-producing and H202-negative lactobacilli. This project will yield new information on lactobacilli as endogenous microbicides and suggest new strategies for prevention of STD's and their sequelae.